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Val⁸-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats

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Val⁸-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats. / Wang, Xiao-Hui; Yang, Wei; Hölscher, Christian et al.

In: Journal of Neuroscience Research, Vol. 91, No. 4, 04.2013, p. 568-577.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Wang, X-H, Yang, W, Hölscher, C, Wang, Z-J, Cai, H-Y, Li, Q-S & Qi, J-S 2013, 'Val⁸-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats', Journal of Neuroscience Research, vol. 91, no. 4, pp. 568-577. https://doi.org/10.1002/jnr.23181

APA

Wang, X-H., Yang, W., Hölscher, C., Wang, Z-J., Cai, H-Y., Li, Q-S., & Qi, J-S. (2013). Val⁸-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats. Journal of Neuroscience Research, 91(4), 568-577. https://doi.org/10.1002/jnr.23181

Vancouver

Wang X-H, Yang W, Hölscher C, Wang Z-J, Cai H-Y, Li Q-S et al. Val⁸-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats. Journal of Neuroscience Research. 2013 Apr;91(4):568-577. doi: 10.1002/jnr.23181

Author

Wang, Xiao-Hui ; Yang, Wei ; Hölscher, Christian et al. / Val⁸-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats. In: Journal of Neuroscience Research. 2013 ; Vol. 91, No. 4. pp. 568-577.

Bibtex

@article{707c57345d3e4b6bbe2544451197f496,
title = "Val⁸-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats",
abstract = "Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD) in the elderly. Glucagon-like peptide-1 (GLP-1), a modulator in T2DM therapy, has been shown to have neuroprotective properties. However, the native GLP-1 can be rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV); the neuroprotective mechanism of GLP-1 in the central nervous system is still an open question, and whether GLP-1 can prevent amyloid β (Aβ)-induced synaptic dysfunction and calcium disorder is still unclear. The present study, by using patch clamp and calcium imaging techniques, investigated the effects of Val⁸-GLP-1(7-36), a GLP-1 analogue with profound resistance to DPP IV, on the excitatory and inhibitory synaptic transmission and intracellular calcium concentration ([Ca²⁺](i) ) in the absence or presence of Aβ1-40. The results showed that 1) Aβ1-40 significantly reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in CA1 pyramidal neurons of rat brain slices; 2) Val⁸-GLP-1(7-36) did not affect the activity of miniature postsynaptic currents but effectively protected against the Aβ1-40-induced decrease in mEPSC and mIPSC frequency; 3) Aβ1-40 significantly increased [Ca²⁺](i) in primary neuronal cultures; and 4) Val⁸-GLP-1(7-36) alone did not change the intracellular calcium level but prevented Aβ1-40-induced persistent elevation of [Ca²⁺](i). These findings demonstrate for the first time that central application of Val⁸-GLP-1(7-36) could protect against Aβ-induced synaptic dysfunction and intracellular calcium overloading, suggesting that the neuroprotection of GLP-1 may be involved in the remodeling of synaptic activity and intracellular calcium homeostasis in the brain.",
keywords = "Amyloid beta-Peptides, Animals, CA1 Region, Hippocampal, Calcium, Cells, Cultured, Cerebral Cortex, Excitatory Postsynaptic Potentials, Glucagon-Like Peptide 1, Homeostasis, Inhibitory Postsynaptic Potentials, Miniature Postsynaptic Potentials, Neurons, Peptide Fragments, Rats, Rats, Wistar, Synapses, Synaptic Transmission",
author = "Xiao-Hui Wang and Wei Yang and Christian H{\"o}lscher and Zhao-Jun Wang and Hong-Yan Cai and Qing-Shan Li and Jin-Shun Qi",
note = "Copyright {\textcopyright} 2013 Wiley Periodicals, Inc.",
year = "2013",
month = apr,
doi = "10.1002/jnr.23181",
language = "English",
volume = "91",
pages = "568--577",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Val⁸-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats

AU - Wang, Xiao-Hui

AU - Yang, Wei

AU - Hölscher, Christian

AU - Wang, Zhao-Jun

AU - Cai, Hong-Yan

AU - Li, Qing-Shan

AU - Qi, Jin-Shun

N1 - Copyright © 2013 Wiley Periodicals, Inc.

PY - 2013/4

Y1 - 2013/4

N2 - Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD) in the elderly. Glucagon-like peptide-1 (GLP-1), a modulator in T2DM therapy, has been shown to have neuroprotective properties. However, the native GLP-1 can be rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV); the neuroprotective mechanism of GLP-1 in the central nervous system is still an open question, and whether GLP-1 can prevent amyloid β (Aβ)-induced synaptic dysfunction and calcium disorder is still unclear. The present study, by using patch clamp and calcium imaging techniques, investigated the effects of Val⁸-GLP-1(7-36), a GLP-1 analogue with profound resistance to DPP IV, on the excitatory and inhibitory synaptic transmission and intracellular calcium concentration ([Ca²⁺](i) ) in the absence or presence of Aβ1-40. The results showed that 1) Aβ1-40 significantly reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in CA1 pyramidal neurons of rat brain slices; 2) Val⁸-GLP-1(7-36) did not affect the activity of miniature postsynaptic currents but effectively protected against the Aβ1-40-induced decrease in mEPSC and mIPSC frequency; 3) Aβ1-40 significantly increased [Ca²⁺](i) in primary neuronal cultures; and 4) Val⁸-GLP-1(7-36) alone did not change the intracellular calcium level but prevented Aβ1-40-induced persistent elevation of [Ca²⁺](i). These findings demonstrate for the first time that central application of Val⁸-GLP-1(7-36) could protect against Aβ-induced synaptic dysfunction and intracellular calcium overloading, suggesting that the neuroprotection of GLP-1 may be involved in the remodeling of synaptic activity and intracellular calcium homeostasis in the brain.

AB - Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD) in the elderly. Glucagon-like peptide-1 (GLP-1), a modulator in T2DM therapy, has been shown to have neuroprotective properties. However, the native GLP-1 can be rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV); the neuroprotective mechanism of GLP-1 in the central nervous system is still an open question, and whether GLP-1 can prevent amyloid β (Aβ)-induced synaptic dysfunction and calcium disorder is still unclear. The present study, by using patch clamp and calcium imaging techniques, investigated the effects of Val⁸-GLP-1(7-36), a GLP-1 analogue with profound resistance to DPP IV, on the excitatory and inhibitory synaptic transmission and intracellular calcium concentration ([Ca²⁺](i) ) in the absence or presence of Aβ1-40. The results showed that 1) Aβ1-40 significantly reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in CA1 pyramidal neurons of rat brain slices; 2) Val⁸-GLP-1(7-36) did not affect the activity of miniature postsynaptic currents but effectively protected against the Aβ1-40-induced decrease in mEPSC and mIPSC frequency; 3) Aβ1-40 significantly increased [Ca²⁺](i) in primary neuronal cultures; and 4) Val⁸-GLP-1(7-36) alone did not change the intracellular calcium level but prevented Aβ1-40-induced persistent elevation of [Ca²⁺](i). These findings demonstrate for the first time that central application of Val⁸-GLP-1(7-36) could protect against Aβ-induced synaptic dysfunction and intracellular calcium overloading, suggesting that the neuroprotection of GLP-1 may be involved in the remodeling of synaptic activity and intracellular calcium homeostasis in the brain.

KW - Amyloid beta-Peptides

KW - Animals

KW - CA1 Region, Hippocampal

KW - Calcium

KW - Cells, Cultured

KW - Cerebral Cortex

KW - Excitatory Postsynaptic Potentials

KW - Glucagon-Like Peptide 1

KW - Homeostasis

KW - Inhibitory Postsynaptic Potentials

KW - Miniature Postsynaptic Potentials

KW - Neurons

KW - Peptide Fragments

KW - Rats

KW - Rats, Wistar

KW - Synapses

KW - Synaptic Transmission

U2 - 10.1002/jnr.23181

DO - 10.1002/jnr.23181

M3 - Journal article

C2 - 23335292

VL - 91

SP - 568

EP - 577

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 4

ER -